Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study
Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study
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DOI：
10.1016/s1473-3099(15)00424-7
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发表时间：
2016-02-01
影响因子：
56.3
通讯作者：
Shen, Jianzhong
中科院分区：
文献类型：
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作者：
Liu, Yi-Yun;Wang, Yang;Shen, Jianzhong
背景到目前为止，多粘菌素耐药涉及染色体突变，但从未报道过通过水平基因转移。在我国食品动物源大肠埃希菌耐药性的常规监测项目中，发现大肠埃希菌对粘菌素的耐药性显著增加。当从猪中分离出一株具有粘菌素耐药性并可转移至另一株的大肠杆菌菌株SHP 45时，我们对可能的质粒介导的多粘菌素耐药性进行了进一步分析。在此，我们报道了第一个质粒介导的多粘菌素耐药机制，MCR-1，在Enterobacteriaceae.方法大肠杆菌SHP 45菌株中的mcr-1基因的全质粒测序和亚克隆鉴定。通过序列比较、同源性建模和电喷雾电离质谱法进行MCR-1机制研究。在2011年4月至2014年11月期间从5个省采集的大肠埃希菌和肺炎克雷伯菌菌株中研究了mcr-1的流行率。MCR-1的能力，赋予多粘菌素耐药在体内进行了检查，在小鼠大腿model.Findings多粘菌素耐药被证明是奇异的，由于质粒介导的mcr-1基因。携带mcr-1的质粒通过接合以10（-1）至10（-3）个细胞/受体细胞的频率动员至大肠杆菌受体，并在肺炎克雷伯菌和铜绿假单胞菌中维持。在体内模型中，MCR-1的产生否定了粘菌素的疗效。MCR-1是磷酸乙醇胺转移酶家族的成员，在大肠杆菌中表达，导致磷酸乙醇胺添加到脂质A中。我们在2011- 2014年期间从523份生肉样本中的78份（15%）和804份动物样本中的166份（21%）以及1322份住院感染患者样本中的16份（1%）中观察到大肠杆菌分离株携带mcr-1。虽然目前仅限于中国，但MCR-1可能会模仿其他全球耐药机制，如NDM-1。我们的研究结果强调，迫切需要采取协调一致的全球行动，打击泛耐药革兰氏阴性菌。
Background Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae.Methods The mcr-1 gene in E coli strain SHP45 was identified by whole plasmid sequencing and subcloning. MCR-1 mechanistic studies were done with sequence comparisons, homology modelling, and electrospray ionisation mass spectrometry. The prevalence of mcr-1 was investigated in E coli and Klebsiella pneumoniae strains collected from five provinces between April, 2011, and November, 2014. The ability of MCR-1 to confer polymyxin resistance in vivo was examined in a murine thigh model.Findings Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10(-1) to 10(-3) cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011-14, and 16 (1%) of 1322 samples from inpatients with infection.Interpretation The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria.